Humanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization
Abstract Despite improvements in pre-clinical drug testing models, predictability of clinical outcomes continues to be inadequate and costly due to poor evidence of drug metabolism. Humanized miniature organs integrating decellularized rodent organs with tissue specific cells are translational model...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2018-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-018-25883-x |
| _version_ | 1818858004896808960 |
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| author | Duong T. Nguyen Matthew O’Hara Cecilia Graneli Ryan Hicks Tasso Miliotis Ann-Christin Nyström Sara Hansson Pia Davidsson Li-Ming Gan Maria Chiara Magnone Magnus Althage Sepideh Heydarkhan-Hagvall |
| author_facet | Duong T. Nguyen Matthew O’Hara Cecilia Graneli Ryan Hicks Tasso Miliotis Ann-Christin Nyström Sara Hansson Pia Davidsson Li-Ming Gan Maria Chiara Magnone Magnus Althage Sepideh Heydarkhan-Hagvall |
| author_sort | Duong T. Nguyen |
| collection | DOAJ |
| description | Abstract Despite improvements in pre-clinical drug testing models, predictability of clinical outcomes continues to be inadequate and costly due to poor evidence of drug metabolism. Humanized miniature organs integrating decellularized rodent organs with tissue specific cells are translational models that can provide further physiological understanding and evidence. Here, we evaluated 4-Flow cannulated rat hearts as the fundamental humanized organ model for cardiovascular drug validation. Results show clearance of cellular components in all chambers in 4-Flow hearts with efficient perfusion into both coronary arteries and cardiac veins. Furthermore, material characterization depicts preserved organization and content of important matrix proteins such as collagens, laminin, and elastin. With access to the complete vascular network, different human cell types were delivered to show spatial distribution and integration into the matrix under perfusion for up to three weeks. The feature of 4-Flow cannulation is the preservation of whole heart conformity enabling ventricular pacing via the pulmonary vein as demonstrated by noninvasive monitoring with fluid pressure and ultrasound imaging. Consequently, 4-Flow hearts surmounting organ mimicry challenges with intact complexity in vasculature and mechanical compliance of the whole organ providing an ideal platform for improving pre-clinical drug validation in addition to understanding cardiovascular diseases. |
| first_indexed | 2024-12-19T08:49:24Z |
| format | Article |
| id | doaj.art-4df7ae2b4a4f4e15a84d4f112a0c0c0b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T08:49:24Z |
| publishDate | 2018-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-4df7ae2b4a4f4e15a84d4f112a0c0c0b2022-12-21T20:28:45ZengNature PortfolioScientific Reports2045-23222018-05-018111010.1038/s41598-018-25883-xHumanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and RecellularizationDuong T. Nguyen0Matthew O’Hara1Cecilia Graneli2Ryan Hicks3Tasso Miliotis4Ann-Christin Nyström5Sara Hansson6Pia Davidsson7Li-Ming Gan8Maria Chiara Magnone9Magnus Althage10Sepideh Heydarkhan-Hagvall11Cardiovascular, Renal and Metabolic Diseases, Innovative Medicines and Early Development Biotech UnitCardiovascular, Renal and Metabolic Diseases, Innovative Medicines and Early Development Biotech UnitSchool of Bioscience, Systems Biology Research Center, University of SkövdeDiscovery Sciences, Innovative Medicines and Early Development Biotech UnitCardiovascular, Renal and Metabolic Diseases, Innovative Medicines and Early Development Biotech UnitCardiovascular, Renal and Metabolic Diseases, Innovative Medicines and Early Development Biotech UnitCardiovascular, Renal and Metabolic Diseases, Innovative Medicines and Early Development Biotech UnitCardiovascular, Renal and Metabolic Diseases, Innovative Medicines and Early Development Biotech UnitEarly Clinical and Development, Innovative Medicines and Early Development Biotech UnitCardiovascular, Renal and Metabolic Diseases, Innovative Medicines and Early Development Biotech UnitCardiovascular, Renal and Metabolic Diseases, Innovative Medicines and Early Development Biotech UnitCardiovascular, Renal and Metabolic Diseases, Innovative Medicines and Early Development Biotech UnitAbstract Despite improvements in pre-clinical drug testing models, predictability of clinical outcomes continues to be inadequate and costly due to poor evidence of drug metabolism. Humanized miniature organs integrating decellularized rodent organs with tissue specific cells are translational models that can provide further physiological understanding and evidence. Here, we evaluated 4-Flow cannulated rat hearts as the fundamental humanized organ model for cardiovascular drug validation. Results show clearance of cellular components in all chambers in 4-Flow hearts with efficient perfusion into both coronary arteries and cardiac veins. Furthermore, material characterization depicts preserved organization and content of important matrix proteins such as collagens, laminin, and elastin. With access to the complete vascular network, different human cell types were delivered to show spatial distribution and integration into the matrix under perfusion for up to three weeks. The feature of 4-Flow cannulation is the preservation of whole heart conformity enabling ventricular pacing via the pulmonary vein as demonstrated by noninvasive monitoring with fluid pressure and ultrasound imaging. Consequently, 4-Flow hearts surmounting organ mimicry challenges with intact complexity in vasculature and mechanical compliance of the whole organ providing an ideal platform for improving pre-clinical drug validation in addition to understanding cardiovascular diseases.https://doi.org/10.1038/s41598-018-25883-x |
| spellingShingle | Duong T. Nguyen Matthew O’Hara Cecilia Graneli Ryan Hicks Tasso Miliotis Ann-Christin Nyström Sara Hansson Pia Davidsson Li-Ming Gan Maria Chiara Magnone Magnus Althage Sepideh Heydarkhan-Hagvall Humanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization Scientific Reports |
| title | Humanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization |
| title_full | Humanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization |
| title_fullStr | Humanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization |
| title_full_unstemmed | Humanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization |
| title_short | Humanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization |
| title_sort | humanizing miniature hearts through 4 flow cannulation perfusion decellularization and recellularization |
| url | https://doi.org/10.1038/s41598-018-25883-x |
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